Terminal deoxynucleotidyl transferase, an unusual DNA polymerase which does not accept template instruction and originally thought to be present only in thymus cells, has now been detected in normal bone marrow cells. This enzyme activity is highly elevated in bone marrow and peripheral blood of patients with types of human leukemia as well as in some human lymphoblastoid cell lines. The proposed project will examine two aspects of terminal transferase activity in normal bone marrow: a) can a specific cell type be identified which contains high levels of this enzyme activity? and b) what happens to terminal transferase activity when bone marrow cells differentiate? Embryonic thymus cells will also be studied to determine the fate of terminal transferase activity during thymus differentiation. Biological experiments with lymphoblastoid cell lines will examine variations in this enzyme activity during periods of DNA metabolism in synchronized cells. The results of these experiments may be useful in characterization and treatment of certain types of human leukemia.